Iodine is an essential trace element, mainly due to the absolute requirement of the thyroid gland for this substance in hormonogenesis. Iodine deficiency disorders (IDD) which include cretinism mental retardation, impaired physical growth and endemic goiter affect hundreds of millions of people worldwide, in both developing and developed countries. Iodine deficiency is exacerbated in pregnant and lactating women, due to increased iodine requirements for formation of the fetal iodine pool, increased maternal renal clearance, and iodine sequestration by the breast and excretion in milk. In the fetus and infant, the requirement for iodine is especially critical because of its accelerated turnover in the thyroid gland, and since iodine mediates a wide range of developmental processes including mental development, skeletal growth and fusion, and lung maturation. The effects of iodine deficiency upon mammogenesis and lactogenesis including quality and breast tissue exceeds that of the thyroid gland. The question of whether the breast is affected locally by iodine also has never been addressed; in the thyroid, iodine levels control both iodine and amino acid uptake. Since mother's milk is the sole source of available iodine for the exclusively breast-fed infant, these issues are of clinical significance. Iodized oil injection is a widely-used therapeutic agent administered to large segments of populations in regions of endemic goiter. The fate of this bolus of iodine in women of reproductive ge is unknown; hence, the question of how the developing fetus or suckling neonate is affected must be raised. We therefore propose to induce iodine deficiency in weanling female rats, feeding them Low Iodine AIN-76C, and Controls, AIN-76C (nutritionally complete diets, in contrast to those previously used in such studies). We will examine serum thyroid gland and breast tissue for iodine and thyroid hormone content; mammary gland growth and differentiation; and general parameters of growth in both dams and their offspring; and assess milk production, quality, and hormonal content. Mammary gland explants and isolated mammary epithelia will be used to examine regulation of iodine uptake in the breast, and the effects of iodine concentration on amino acid uptake. We will further examine the effects of maternal iodized oil injection on maternal, fetal, and neonatal thyroid function and tissue development in dams injected at pre-, mid- or late gestation, and perform cross-fostering experiments to distinguish immediate (fetal) from longer-term (neonatal) effects upon the infant.